The effect of PGI2, the principal metabolite of arachidonic acid in mammalian arterial and venous tissues, on renal function and renin secretion was investigated in anesthetized, hypophysectomized dogs undergoing a maximal water diuresis. PGI2 in a concentration of 0.04 microng/kg/min (a concentration not causing vasodepressor effects) increased urine flow and urinary sodium excretion in the absence of changes in glomerular filtration rate or renal plasma flow. The fact that PGI2 significantly increased free water clearance and distal delivery of sodium and inhibited distal reabsorption of glomerular filtrate is suggestive of a direct effect on proximal as well as distal sites of the nephron. PGI2 increased renin secretion rates three-fold. The data support a direct effect of PGI2 on renin release. On a molar basis, PGI2 is about 10 times more potent than PGE2 with regard to natriuresis, diuresis and renin release. Thus, PGI2 may be the major prostaglandin involved in the regulation of salt and water excretion.